Newly developed methods for lymphoid cell analysis, growth in culture and cloning offer the promise of more effective strategies for the control of malignancy. Experimental models are required to test and refine these potential treatments and determine their applicability to naturally occurring cancers. In a unique model system developed in our laboratory, leukemia in mice undergoes predictable immunologically mediated spontaneous regression. Leukemia regression is efficiently induced in progressor leukemic mice with lymphoid cells from regressed animals. Our aims are to use this model to identify the cells responsible for transfer of leukemia regression, to isolate and clone these cells, to define their specificity and mechanism, and to determine whether immunological treatment can be used to prevent disease recurrence. Using spleen cells from either regressed or immunized mice, we have cultured and cloned T cells that are significantly reactive against viral antigens. Experiments are currently in progress to determine the exact specificity and phenotype of the cloned cells, as well as their immunotherapeutic value in preventing leukemia recurrence in vivo.